Predictors of Chronic Kidney Disease In Type 1 Diabetes

CKD risk not necessarily tied to albuminuria in patients with type 1 diabetes.

The International Diabetes Federation Diabetes Atlas estimated that by 2040 approximately 642 million people worldwide will be afflicted with diabetes. The incidence of type 1 diabetes, especially in children, continues to grow at a rate of 3% annually worldwide. Type 1 diabetes accounts for 7-12% of all diabetes cases globally.

One of the leading causes of morbidity and mortality in patients with diabetes is related to kidney disease. Chronic kidney disease is the major precipitating factor to end-stage renal disease and is associated with an increased risk for cardiovascular events, which remains the leading cause of death in patients with type 1 diabetes.

Retaining renal function in the diabetes patient population is a major goal for healthcare practitioners and regular evaluations of kidney function helps mitigate the risk of disease progression and gives practitioners the opportunity to intervene early. Increases in urinary albumin excretion rate (AER) is an early indicator of renal damage and may promote progression to macroalbuminuria and eventual decrease in glomerular filtration rate. However, recent studies have shown that a significant number of patients with type 1 diabetes are progressing to end-stage renal disease in the absence of albuminuria.

Researchers retrospectively analyzed over 2,600 patients with type 1 diabetes and normal renal function at baseline to evaluate predictors for the development of depressed renal function with or without albuminuria, or its single components, and their relationship with traditional risk factors.1 The primary outcome was the development of chronic kidney disease over the 5-year study and secondary outcomes included the development of macroalbuminuria, microalbuminuria and decreased eGFR. There was a total of 2,656 participants of which 56% were male, the mean age was 44 +/- 14 years, the mean duration of diabetes was 17 +/- 12 years, and the average BMI was 24.4 +/- 3.4 kg/m2. The majority of patients were at a normal body weight, however glycemic control was poor across the cohort with a mean HbA1c of 7.7%. However, the lipid and blood pressure profiles of the patients were relatively low with a mean LDL of 110 mg/dL and a mean blood pressure of 125/76. By study design all patients were required to have normal urine albumin excretion and eGFR ≥ 60mL/min/1.73m2 therefore, the average baseline eGFR was 90 +/- 16 mL/min/1.73m2.

Over the 5-year follow-up period 21% (n=559) of patients developed CKD, 4.3% (n=115) had an eGFR < 60 mL/min/1.73m2 and 18% developed albuminuria. Patients who developed CKD or had significantly diminished eGFR were older, had a longer history of diabetes, had poorer glycemic control and higher blood pressure values in comparison to other participants within the cohort. There was an association between higher baseline triglyceride levels and the development of CKD, and as expected patients with diminished eGFR had lower baseline eGFRs in comparison to patients who did not show a diminished eGFR. Utilizing multivariate logistic analysis, researchers investigated the relationship between the onset of decreased kidney function with or without the presence of albuminuria and the presence of other cardiovascular risks. Age independently affected the reduction in eGFR with a 10-year risk increase of 95% (double the risk for younger patients), while duration of disease independently affected the presence of albuminuria with a 10-year risk increase of 1.5%. It should be noted that researchers did not find any statistically significant differences between the two genders.

Glycemic control had a significant impact on the onset of albuminuria with a 16% increased risk of albuminuria for every 1% increase in HbA1c, however this did not show an effect on eGFR. Based on these findings, researchers estimated that over a 5-year follow-up approximately 1 out of every 5 type 1 diabetes patients attending diabetes centers in Italy will develop CKD. The results of this study were in agreeance with previous studies that showed development of albuminuria increases the chances of a patient developing CKD. However, it should be noted that poorer glycemic control, and not the development of albuminuria, played a more significant role in the development of CKD. Multivariate models showed a 13% greater risk for the development of CKD and a 16% greater risk for albuminuria for each 1% increase in HbA1c. There was not a statistically significant association between glycemic control and reduction in eGFR. This finding clearly supports the need for tighter glycemic control in patients with type 1 diabetes and reinforces the need to achieve a HbA1c <7%.

Practice Pearls:

21% of patients with type 1 diabetes with normal renal function developed CKD

For every 1% increase in HbA1c there was a 13% increase in development of CKD

Elevated triglyceride levels were correlated to the development of CKD